Our main objective is to elucidate the contribution of prefrontal cortex and striatum as an integrated circuit in inhibitory control. Inhibitory control is conceptualized as a form of cognitive control, which refers to an individual's ability to avoid inappropriate actions in a given situation. While the prefrontal cortex (PFC) has been postulated to play a central role in inhibitory control, accumulating evidence suggests that it is part of a distributed network. People with lesions in the frontal lobes and striatum are more vulnerable to distractions and are less able to inhibit actions that are no longer relevant to the current goal. Research in both humans and animals has shown that frontal and striatal areas have close anatomical connections and exhibit activity closely related to the learning and control of goal-directed behaviors. Recent neuroimaging research has made substantial advances in understanding the role of prefrontal cortex in inhibiting manual responses to visual cues and, in particular, the right inferior PFC has been proposed to serve as a general-purpose inhibitory mechanism. In contrast, animal research has suggested a modality specific mechanism for inhibiting unwanted eye movements. The novel contribution of this project is to examine modality effects by studying manual and oculomotor inhibition in the same human subjects. We will use functional magnetic resonance imaging (fMRI) to record brain activity while human subjects perform a stop-signal task. This task requires them to generate a specific response to a go signal and occasionally cancel the planned response when a stop signal appears. We will compare and contrast frontal and striatal activity during inhibition of planned eye versus hand movements. We hypothesize that while the oculomotor and motor systems may use similar mechanisms to cancel planned movements, inhibitory control is not a unified process, but involves different fronto-striatal circuits as implicated by the animal research. The outcome of this initial study will serve as a framework for future studies of interactions between frontal and striatal areas during inhibitory control. Knowing about the precise architecture of the neural circuitry for response inhibition will have implications for the localization and specificity of treatment for disorders associated with poor inhibitory control such as drug addiction. [unreadable] [unreadable] [unreadable]